The goal of these studies is to optimize a well-studied protocol for the induction of specific allograft prolongation that requires neither extensive donor pretreatment nor chronic immunosuppression. In this procedure recipients are treated with a short-term course of antilymphocyte serum (ALS) followed by an injection of donor bone marrow cells. Mice treated in this fashion exhibit a state of specific allograft unresponsiveness mediated at least in part by donor-derived suppressor cells. Successful application of this system to renal allografts in dogs, and monkeys has been achieved, and recent application to man suggests an important clinical feasibility. Our laboratory has extensively characterized, and prepared fractions highly enriched for the bone marrow cell active in the prolongation of allografts. The injection of fractionated bone marrow has been shown to be superior to unfractionated bone marrow as measured by the extent of graft prolonging ability. Proposed experiments seek (1) to optimize the ALS/fractionated bone marrow protocol in canine renal allograft experiments by including cyclosporin A in the treatment protocol; (2) to expand the application of neonatal tissue allografts which have been shown to exhibit superior survival in the ALS and bone marrow system; (3) to define optimal homing patterns of injected bone marrow for the purpose of targeting active cells to relevant sites; (4) to study the nature of cellular interaction during the immediate posttreatment period in recipient animals; and (5) to produce a monoclonal antibody to cell-surface markers unique to the active bone marrow cell. In addition to continuing the clinically relevant studies in dogs, experiments will be performed in skin and islet allograft models in mice. Promising results from the small animal studies will be immediately tested in the canine renal allograft model. Long-term clinical and immunological follow up in dogs should provide insight into the application of these protocols to man.